Poorly treated pain in older adults is a critical public health problem. When compared to young adults, evidence suggests that older adults have more painful diagnoses, have increased sensory thresholds for pain, and are at risk for under treatment of their pain. Sex associated differences in the experience of pain are reported in the literature with women generally experiencing more pain and reporting increased sensitivity. Poorly treated pain leads to many associated symptoms, negatively impacts quality of life, and increases health care costs. Exploring the biological reasons for alterations in pain processing is essential to increasing our understanding about pain in older adults. The paucity of neurobiological evidence to support best practice pain management in older adults places these individuals at risk for poor pain management practices. The goals of this project are to determine sex and age associated psychophysical and neurophysiological differences in the processing of pain. Our pilot data in a sample of 12 male and 12 female (age-matched) healthy older adults (ages 65-81) suggests that in response to thermal pain, increasing age is associated with increased brain activation and reduced unpleasantness only in females. Using psychophysics (to measure sensory threshold and affective unpleasantness) and fMRI blood oxygenation level dependent (BOLD) methods (to measure stimulus-evoked brain activation), we will examine age-associated differences in thermal pain processing and their underlying neurophysiology in a broad range of healthy adults (age 30-89). We will also acquire resting state functional connectivity data for secondary analyses exploring whether resting state connectivity predicts psychophysical and neurophysiological responses to thermal pain. To control for the effects of altered blood flow associated with aging, we will acquire resting state arterial spin labeling MRI (ASL) data to quantify resting cerebral blood flow (CBF). We will interpret findings in the context of a proposed neural model of pain, aging, and sex. Our overall hypothesis is that age-associated nervous system changes lead to alterations in inhibitory circuits that modulate pain associated unpleasantness which place older adults, especially females, at reduced risk for detection of pain upon injury, increased risk for under treatment of pain, and increased risk for chronic pain. Altered sensory and affective processing has implications for age-related and sex-specific pain assessment and management strategies. Recent advancements in assessing experimental pain using fMRI provide a critical foundation for our long-term goals which are to determine how aging affects the psychophysics and neurobiology of pain processing and to use this information as normal baseline data for future R01 studies including older adults with painful conditions to inform improved prevention, assessment, and treatment strategies.